Effectiveness of statins on outcomes of patients with Embolic Stroke of Undetermined Source (ESUS).

BACKGROUND: Statins are highly recommended as a secondary prevention strategy after a stroke. Embolic Stroke of Undetermined Source (ESUS) accounts for up to one fifth of cases of ischemic stroke. There is a lack of studies investigating the effectiveness of statins in this subgroup of patients. METHODS: We designed a longitudinal cohort study involving patients properly diagnosed with ESUS. Data about statin therapy included information about the time of initiation of the treatment, pre-stroke statin use, statin withdrawal, and the type and dosage of the statin prescribed. Patients were followed for 48 months after the index stroke. The primary endpoints included stroke recurrence, major cardiovascular events, and death from all causes. The secondary endpoint was the functional outcome, assessed in a standardized and systematic way using the modified Rankin Scale (mRS). RESULTS: Patients who were not taking any statin after ESUS have significantly increased odds of stroke recurrence (OR = 3.29, 95% CI 1.27 - 8.55) or presenting the composite outcome of stroke recurrence, major cardiovascular events, and death (OR = 3.70, 95% CI 1.44 - 9.50) in the multivariate analysis. No statin therapy was directly associated with the functional outcome as well (OR = 3.32, 95% CI = 1.58 - 6.96). The early initiation of the statin therapy was estimated to reduce the risk of a second stroke and the composite outcome by 89% and 87%. CONCLUSIONS: Our pioneering study provides evidence that patients with ESUS may benefit from statin therapy, especially if prescribed early and at higher dosages.

Rivaroxaban for Stroke Prevention after Embolic Stroke of Undetermined Source.

BACKGROUND: Embolic strokes of undetermined source represent 20% of ischemic strokes and are associated with a high rate of recurrence. Anticoagulant treatment with rivaroxaban, an oral factor Xa inhibitor, may result in a lower risk of recurrent stroke than aspirin. METHODS: We compared the efficacy and safety of rivaroxaban (at a daily dose of 15 mg) with aspirin (at a daily dose of 100 mg) for the prevention of recurrent stroke in patients with recent ischemic stroke that was presumed to be from cerebral embolism but without arterial stenosis, lacune, or an identified cardioembolic source. The primary efficacy outcome was the first recurrence of ischemic or hemorrhagic stroke or systemic embolism in a time-to-event analysis; the primary safety outcome was the rate of major bleeding. RESULTS: A total of 7213 participants were enrolled at 459 sites; 3609 patients were randomly assigned to receive rivaroxaban and 3604 to receive aspirin. Patients had been followed for a median of 11 months when the trial was terminated early because of a lack of benefit with regard to stroke risk and because of bleeding associated with rivaroxaban. The primary efficacy outcome occurred in 172 patients in the rivaroxaban group (annualized rate, 5.1%) and in 160 in the aspirin group (annualized rate, 4.8%) (hazard ratio, 1.07; 95% confidence interval [CI], 0.87 to 1.33; P=0.52). Recurrent ischemic stroke occurred in 158 patients in the rivaroxaban group (annualized rate, 4.7%) and in 156 in the aspirin group (annualized rate, 4.7%). Major bleeding occurred in 62 patients in the rivaroxaban group (annualized rate, 1.8%) and in 23 in the aspirin group (annualized rate, 0.7%) (hazard ratio, 2.72; 95% CI, 1.68 to 4.39; P<0.001). CONCLUSIONS: Rivaroxaban was not superior to aspirin with regard to the prevention of recurrent stroke after an initial embolic stroke of undetermined source and was associated with a higher risk of bleeding. (Funded by Bayer and Janssen Research and Development; NAVIGATE ESUS ClinicalTrials.gov number, NCT02313909 .).

The influence of statin withdrawal and adherence on stroke outcomes.

INTRODUCTION: With multiple proven benefits, statin therapy has become the most critical advance in stroke prevention. We aimed to evaluate the risk factors and the effect of poor adherence or statin interruption on the clinical outcomes of ischemic stroke. METHODS: This prospective cohort study included patients admitted with acute ischemic stroke between 2014 and 2018. Consecutive patients were distinguished into subgroups according to the adherence and withdrawal of statin. All participants were followed for 24 months. The outcomes included stroke recurrence, major cardiovascular events, all-cause mortality, and functional performance. Functional outcome was assessed using the modified Rankin Scale at 7 days, 30 days, 6 months, and 2 years after hospital admission for ischemic stroke. In a secondary analysis, outcome variables were compared with statin-naïve patients. RESULTS: We included 479 patients with acute ischemic stroke. The mean age was 58.3, and 55.0% were male. There were 96 (21.8%) patients who received no statin, 150 (34.9%) patients with poor adherence, 40 (9.1%) patients with intermediate adherence, and 154 (35.0%) patients with good adherence. There were 54 (15.7%) cases of withdrawal of treatment. Patients with hypertension, previous stroke, and large-artery atherosclerosis were associated with poor adherence (p < 0.05). Those with poor adherence were significantly associated with worse functional outcomes and a higher incidence of stroke recurrence (p < 0.05). Significant functional recovery was just seen in patients with satisfactory adherence. CONCLUSION: The suboptimal use of statins is associated with significantly worse clinical outcomes in stroke patients.

Prevalence and Predictors of Fatigue and Neuropsychiatric Symptoms in Patients with Minor Ischemic Stroke.

OBJECTIVES: Patients who are victims of a mild stroke are vulnerable to several invisible and neglected neurological sequelae. In parallel, it is known that fatigue and neuropsychiatric symptoms are common complications after a stroke in general. Our aim was to describe the prevalence and the factors associated with these two outcomes after a minor stroke. MATERIALS AND METHODS: We conducted a prospective observational cohort study that included consecutive patients diagnosed with minor ischemic stroke between 2015 and 2019. Minor stroke was defined as NIHSS < 4 and modified Rankin Scale (mRS) < 2. Patients were followed for 12 months after the index stroke. The primary endpoints included fatigue and neuropsychiatric impairment, which were evaluated with the Fatigue Severity Scale (FSS) and the Hospital Anxiety Depression Scale (HADS), respectively. RESULTS: A total of sixty patients were followed in our cohort. The mean age was 53.0 (SD 15.0) and 51.7% were male. There were 32 (53.3%) and 25 (41.7%) patients who developed PSF and post-stroke neuropsychiatric symptoms, respectively. The use of antidepressants and statins were associated with post-stroke fatigue, while women and younger patients were more likely to develop neuropsychiatric symptoms after the stroke (p < 0.05). Eighteen (30.0%) patients were diagnosed with both post-stroke fatigue and psychiatric disorders. CONCLUSIONS: Post-stroke fatigue and neuropsychiatric symptoms are prevalent in minor stroke and should be independently addressed as a part of the recovery goal.

The influence of statins on the risk of post-stroke epilepsy.

BACKGROUND: Currently, statins are widely used for secondary prevention of stroke due to their pleiotropic neuroprotective effects. Epilepsy is a common complication of cerebrovascular diseases. The purpose of this study was to evaluate the effect of statin therapy on the occurrence of post-stroke epilepsy (PSE). METHODS: In this prospective cohort study, patients who suffered an ischemic stroke and without history of epilepsy before stroke were enrolled. At baseline, patients were classified according to the particularities of statin therapy. Statin use onset and adherence to treatment were registered as well. After a follow-up period of 1 year, we assessed the occurrence of seizures and PSE. RESULTS: Among the 477 patients included in our cohort, there were 91 (19.1%) patients without statins, 160 (33.5%) with simvastatin 20 mg, 180 (37.7%) with simvastatin 40 mg, and 46 (9.6%) with high-potency statins. Overall, PSE emerged in 53 (11.1%) patients. PSE was significantly more prevalent among those who did not receive statins and those with lower doses of simvastatin. Acute onset of statin use was associated with reduced odds of having PSE. CONCLUSION: Adequate treatment with statins after stroke may lower the risk of PSE.

Stroke Care Trends During COVID-19 Pandemic in Zanjan Province, Iran. From the CASCADE Initiative: Statistical Analysis Plan and Preliminary Results.

BACKGROUND: The emergence of the COVID-19 pandemic has significantly impacted global healthcare systems and this may affect stroke care and outcomes. This study examines the changes in stroke epidemiology and care during the COVID-19 pandemic in Zanjan Province, Iran. METHODS: This study is part of the CASCADE international initiative. From February 18, 2019, to July 18, 2020, we followed ischemic and hemorrhagic stroke hospitalization rates and outcomes in Valiasr Hospital, Zanjan, Iran. We used a Bayesian hierarchical model and an interrupted time series analysis (ITS) to identify changes in stroke hospitalization rate, baseline stroke severity [measured by the National Institutes of Health Stroke Scale (NIHSS)], disability [measured by the modified Rankin Scale (mRS)], presentation time (last seen normal to hospital presentation), thrombolytic therapy rate, median door-to-needle time, length of hospital stay, and in-hospital mortality. We compared in-hospital mortality between study periods using Cox-regression model. RESULTS: During the study period, 1,026 stroke patients were hospitalized. Stroke hospitalization rates per 100,000 population decreased from 68.09 before the pandemic to 44.50 during the pandemic, with a significant decline in both Bayesian [Beta: -1.034; Standard Error (SE): 0.22, 95% CrI: -1.48, -0.59] and ITS analysis (estimate: -1.03, SE = 0.24, p < 0.0001). Furthermore, we observed lower admission rates for patients with mild (NIHSS < 5) ischemic stroke (p < 0.0001). Although, the presentation time and door-to-needle time did not change during the pandemic, a lower proportion of patients received thrombolysis (-10.1%; p = 0.004). We did not see significant changes in admission rate to the stroke unit and in-hospital mortality rate; however, disability at discharge increased (p < 0.0001). CONCLUSION: In Zanjan, Iran, the COVID-19 pandemic has significantly impacted stroke outcomes and altered the delivery of stroke care. Observed lower admission rates for milder stroke may possibly be due to fear of exposure related to COVID-19. The decrease in patients treated with thrombolysis and the increased disability at discharge may indicate changes in the delivery of stroke care and increased pressure on existing stroke acute and subacute services. The results of this research will contribute to a similar analysis of the larger CASCADE dataset in order to confirm findings at a global scale and improve measures to ensure the best quality of care for stroke patients during the COVID-19 pandemic.

Efficacy and Safety of Rivaroxaban Versus Aspirin in Embolic Stroke of Undetermined Source and Carotid Atherosclerosis.

Background and Purpose- The sources of emboli in patients with embolic stroke of undetermined source (ESUS) are multiple and may not respond uniformly to anticoagulation. In this exploratory subgroup analysis of patients with carotid atherosclerosis in the NAVIGATE (New Approach Rivaroxaban Inhibition of Factor Xa in a Global Trial Versus ASA to Prevent Embolism)-ESUS trial, we assessed whether the treatment effect in this subgroup is consistent with the overall trial population and investigated the association of carotid atherosclerosis with recurrent ischemic stroke. Methods- Carotid atherosclerosis was analyzed either as the presence of mild (ie, 20%-49%) atherosclerotic stenosis or, separately, as the presence of carotid plaque. Primary efficacy outcome was ischemic stroke recurrence. Safety outcomes were major bleeding and symptomatic intracerebral bleeding. Results- Carotid plaque was present in 40% of participants and mild carotid stenosis in 11%. There was no significant difference in ischemic stroke recurrence between rivaroxaban- and aspirin-treated patients among 490 patients with carotid stenosis (5.0 versus 5.9/100 patient-years, respectively, hazard ratio [HR], 0.85; 95% CI, 0.39-1.87; P for interaction of treatment effect with patients without carotid stenosis 0.78) and among 2905 patients with carotid plaques (5.9 versus 4.9/100 patient-years, respectively, HR, 1.20; 95% CI, 0.86-1.68; P for interaction of treatment effect with patients without carotid stenosis 0.2). Among patients with carotid plaque, major bleeding was more frequent in rivaroxaban-treated patients compared with aspirin-treated (2.0 versus 0.5/100 patient-years, HR, 3.75; 95% CI, 1.63-8.65). Patients with carotid stenosis had similar rate of ischemic stroke recurrence compared with those without (5.4 versus 4.9/100 patient-years, respectively, HR, 1.11; 95% CI, 0.73-1.69), but there was a strong trend of higher rate of ischemic stroke recurrence in patients with carotid plaque compared with those without (5.4 versus 4.3/100 patient-years, respectively, HR, 1.23; 95% CI, 0.99-1.54). Conclusions- In ESUS patients with carotid atherosclerosis, we found no difference in efficacy between rivaroxaban and aspirin for prevention of recurrent stroke, but aspirin was safer, consistent with the overall trial results. Carotid plaque was much more often present ipsilateral to the qualifying ischemic stroke than contralateral, supporting an important etiological role of nonstenotic carotid disease in ESUS. Clinical Trial Registration- URL: https://www.clinicaltrials.gov. Unique identifier: NCT02313909.

Predictors of Recurrent Ischemic Stroke in Patients with Embolic Strokes of Undetermined Source and Effects of Rivaroxaban Versus Aspirin According to Risk Status: The NAVIGATE ESUS Trial.

BACKGROUND: Embolic stroke of undetermined source (ESUS) identifies patients with cryptogenic ischemic stroke presumed due to embolism from several unidentified sources. Among patients with recent ESUS, we sought to determine independent predictors of recurrent ischemic stroke during treatment with aspirin or rivaroxaban and to assess the relative effects of these treatments according to risk. METHODS: Exploratory analyses of 7213 participants in the NAVIGATE ESUS international trial who were randomized to aspirin 100 mg/day or rivaroxaban 15 mg/day and followed for a median of 11 months, during which time there were 309 first recurrent ischemic strokes (4.6% per year). Baseline features were correlated with recurrent stroke by multivariate analysis. RESULTS: The 7 independent predictors of recurrent stroke were stroke or transient ischemic attack (TIA) prior to the qualifying stroke (hazard ratio [HR] 2.03 95% confidence internal [CI] 1.58-2.60), current tobacco user (HR 1.62, 95% CI 1.24-2.12), age (HR 1.02 per year increase, 95%CI 1.01-1.03), diabetes (HR 1.28, 95% CI 1.01-1.64), multiple acute infarcts on neuroimaging (HR 1.49, 95% CI 1.09-2.02), aspirin use prior to qualifying stroke (HR 1.34, 95% CI 1.02-1.70), and time from qualifying stroke to randomization (HR .98, 95% CI .97-.99). The rate of recurrent stroke rate was 2.6% per year for participants without any of these risk factors, and increased by an average of 45% for each independent predictor (P < .001). There were no significant interactions between treatment effects and independent stroke predictors or stroke risk status. CONCLUSIONS: In this large cohort of ESUS patients, several features including prior stroke or TIA, advanced age, current tobacco user, multiple acute infarcts on neuroimaging, and diabetes independently identified those with an increased risk of ischemic stroke recurrence. The relative effects of rivaroxaban and aspirin were similar across the spectrum of independent stroke predictors and recurrent stroke risk status.

Characterization of Patients with Embolic Strokes of Undetermined Source in the NAVIGATE ESUS Randomized Trial.

BACKGROUND: The New Approach Rivaroxaban Inhibition of Factor Xa in a Global Trial vs. ASA to Prevent Embolism in Embolic Stroke of Undetermined Source (NAVIGATE-ESUS) trial is a randomized phase-III trial comparing rivaroxaban versus aspirin in patients with recent ESUS. AIMS: We aimed to describe the baseline characteristics of this large ESUS cohort to explore relationships among key subgroups. METHODS: We enrolled 7213 patients at 459 sites in 31 countries. Prespecified subgroups for primary safety and efficacy analyses included age, sex, race, global region, stroke or transient ischemic attack prior to qualifying event, time to randomization, hypertension, and diabetes mellitus. RESULTS: Mean age was 66.9 ± 9.8 years; 24% were under 60 years. Older patients had more hypertension, coronary disease, and cancer. Strokes in older subjects were more frequently cortical and accompanied by radiographic evidence of prior infarction. Women comprised 38% of participants and were older than men. Patients from East Asia were oldest whereas those from Latin America were youngest. Patients in the Americas more frequently were on aspirin prior to the qualifying stroke. Acute cortical infarction was more common in the United States, Canada, and Western Europe, whereas prior radiographic infarctions were most common in East Asia. Approximately forty-five percent of subjects were enrolled within 30 days of the qualifying stroke, with earliest enrollments in Asia and Eastern Europe. CONCLUSIONS: NAVIGATE-ESUS is the largest randomized trial comparing antithrombotic strategies for secondary stroke prevention in patients with ESUS. The study population encompasses a broad array of patients across multiple continents and these subgroups provide ample opportunities for future research.

Global Survey of the Frequency of Atrial Fibrillation-Associated Stroke: Embolic Stroke of Undetermined Source Global Registry.

BACKGROUND AND PURPOSE: Atrial fibrillation (AF) is increasingly recognized as the single most important cause of disabling ischemic stroke in the elderly. We undertook an international survey to characterize the frequency of AF-associated stroke, methods of AF detection, and patient features. METHODS: Consecutive patients hospitalized for ischemic stroke in 2013 to 2014 were surveyed from 19 stroke research centers in 19 different countries. Data were analyzed by global regions and World Bank income levels. RESULTS: Of 2144 patients with ischemic stroke, 590 (28%; 95% confidence interval, 25.6-29.5) had AF-associated stroke, with highest frequencies in North America (35%) and Europe (33%) and lowest in Latin America (17%). Most had a history of AF before stroke (15%) or newly detected AF on electrocardiography (10%); only 2% of patients with ischemic stroke had unsuspected AF detected by poststroke cardiac rhythm monitoring. The mean age and 30-day mortality rate of patients with AF-associated stroke (75 years; SD, 11.5 years; 10%; 95% confidence interval, 7.6-12.6, respectively) were substantially higher than those of patients without AF (64 years; SD, 15.58 years; 4%; 95% confidence interval, 3.3-5.4; P<0.001 for both comparisons). There was a strong positive correlation between the mean age and the frequency of AF (r=0.76; P=0.0002). CONCLUSIONS: This cross-sectional global sample of patients with recent ischemic stroke shows a substantial frequency of AF-associated stroke throughout the world in proportion to the mean age of the stroke population. Most AF is identified by history or electrocardiography; the yield of conventional short-duration cardiac rhythm monitoring is relatively low. Patients with AF-associated stroke were typically elderly (>75 years old) and more often women.

Thrombus Features in Hyperacute Ischemic Stroke: A Perspective on Using Length and Density Evaluation.

BACKGROUND: More insights in the etiopathogenesis of thrombi could be helpful in the treatment of patients with acute ischemic stroke (AIS). One of the most confident and early imaging findings of stroke includes arterial hyperdensity. The purpose of this study was to determine whether thrombi's density and length would be useful for predicting their origin. METHODS: We evaluated 68 consecutive patients with AIS to correlate the presence of thrombi and their imaging features with the stroke subtype. RESULTS: After excluding patients with small-artery occlusion mechanism and undetermined and other causes, the stroke etiologic subtypes were large-artery atherosclerosis (LAA) in 59.0% of the patients, cardioembolism in 31.0%, and cervical artery dissection (CAD) in 10.0%. CAD more often caused thrombi with the longest length and highest attenuation, while thrombi that originated from the LAA had the smallest length and lowest attenuation. The mean Hounsfield unit (HU) values of all thrombi (with and without hyperdensity) on noncontrast computed tomography were 62.4 (50.0-70.0) in CAD, 53.8 (42.0-65.0) in cardioembolism, and 48.6 (27.0-65.0) in LAA. The length measurements were 28.5 mm (12.0-52.0) in CAD, 13.7 mm (5.0-31.0) in cardioembolism, and 10.8 mm (3.0-25.0) in the LAA subtype. The minimum cutoff value of 60 HU and a length greater than 20 mm were able to discriminate the CAD thrombi with an accuracy of 86.8% and 92.6%, respectively. CONCLUSION: Our study findings show how important thrombus analysis is in patients with AIS. Thrombus analysis can allow early suspicion of CAD before dedicated imaging of the cervical arteries is performed.

The active extravasation of contrast (spot sign) depicted on multidetector computed tomography angiography might predict structural vascular etiology and mortality in secondary intracranial hemorrhage.

OBJECTIVE: Intracerebral hemorrhage (ICH) occurs in 10% to 15% of all strokes and is accompanied by high rates of mortality, disability, and neurological sequelae. Our aim was to assess the presence and prognostic implications of the active extravasation of contrast within the hemorrhage (spot sign) in a series of patients with secondary ICH. METHODS: We analysed 59 subjects who arrived at a tertiary hospital with secondary ICH and a brain parenchyma hemorrhage greater than 2.0 cm in any axis. RESULTS: Spot sign was observed in 11 subjects, including 8 patients with saccular aneurysm, 1 with arteriovenous malformation, 1 with coagulation disorder and 1 with venous sinus thrombosis. A 37.5% mortality rate was documented in the spot sign-negative group, whereas the presence of this imaging finding was followed by an 81.8% in-hospital mortality rate. CONCLUSIONS: Spot sign was correlated with vascular etiology and was a predictor of mortality in our series of patients.

The prognostic significance of the lipid profile after an ischemic stroke.

BACKGROUND: The role that cholesterol levels play in stroke is still uncertain, especially in secondary prevention. The aim was to determine how a comprehensive analysis of the lipid profile can be associated with post-stroke outcomes.Consecutive patients diagnosed with ischemic stroke were included in our cohort and followed up for 24months. Baseline clinical and demographic data were collected as well as a complete lipid profile 6-months after the index stroke. Lipid variables were analyzed quantitatively and qualitatively. Clinical outcomes included stroke recurrence, major cardiovascular events, and functional performance (assessed with the modified Rankin scale). RESULTS: The study included 588 patients with an average age of 58.3 years. There were 148 (25.2%) patients with high total cholesterol, 260 (44.2%) with low HDL, 180 (30.6%) with high LDL, and 204 (34.7%) with high triglycerides. There were 164 (27.9%) patients with no abnormalities in the lipid profile. After the follow-up, 108 (18.3%) had another stroke, 32 (5.4%) had major cardiovascular events, and 360 (61.2%) presented good functional outcomes. A higher LDL-C/HDL-C ratio and a low HDL-C level were significantly associated with worse cardiovascular outcomes. The detection of LDL-C > 70 mg/dL was an independent predictor of a higher risk of stroke recurrence and worse functional performance. The greater the number of altered lipid variables, the greater the chance of developing an unfavorable composite outcome and presenting cardiovascular events after the stroke. CONCLUSIONS: The complete analysis of the lipid panel allows the determination of the prognosis of patients who suffered a stroke.

Ischemic stroke with unknown onset of symptoms: current scenario and perspectives for the future.

BACKGROUND: Stroke is a major cause of disability worldwide and a neurological emergency. Intravenous thrombolysis and mechanical thrombectomy are effective in the reperfusion of the parenchyma in distress, but the impossibility to determine the exact time of onset was an important cause of exclusion from treatment until a few years ago. OBJECTIVES: To review the clinical and radiological profile of patients with unknown-onset stroke, the imaging methods to guide the reperfusion treatment, and suggest a protocol for the therapeutic approach. METHODS: The different imaging methods were grouped according to current evidence-based treatments. RESULTS: Most studies found no difference between the clinical and imaging characteristics of patients with wake-up stroke and known-onset stroke, suggesting that the ictus, in the first group, occurs just prior to awakening. Regarding the treatment of patients with unknown-onset stroke, four main phase-three trials stand out: WAKE-UP and EXTEND for intravenous thrombolysis, and DAWN and DEFUSE-3 for mechanical thrombectomy. The length of the therapeutic window is based on the diffusion weighted imaging-fluid-attenuated inversion recovery (DWI-FLAIR) mismatch, core-penumbra mismatch, and clinical core mismatch paradigms. The challenges to approach unknown-onset stroke involve extending the length of the time window, the reproducibility of real-world imaging modalities, and the discovery of new methods and therapies for this condition. CONCLUSION: The advance in the possibilities for the treatment of ischemic stroke, while guided by imaging concepts, has become evident. New studies in this field are essential and needed to structure the health care services for this new scenario.

ANTECEDENTES: O acidente vascular cerebral (AVC) é uma das principais causas de incapacidade em todo o mundo, e uma emergência neurológica. A trombólise intravenosa e a trombectomia mecânica são eficazes na reperfusão do parênquima em sofrimento, mas a impossibilidade de determinar o tempo exato de início era uma causa importante de exclusão ao tratamento até alguns anos atrás. OBJETIVOS: Revisar o perfil clínico-radiológico dos pacientes com AVC de tempo indeterminado, os métodos de imagem para guiar o tratamento de reperfusão, e sugerir um protocolo para a abordagem terapêutica. MéTODOS: Os diferentes métodos de imagem foram agrupados de acordo com os tratamentos atuais baseados em evidências. RESULTADOS: A maioria dos estudos não encontrou diferença entre as características clínicas e de imagem dos pacientes com AVC reconhecido ao despertar e AVC de tempo definido, o que sugere que o icto, no primeiro grupo, ocorre próximo ao acordar. Quanto ao tratamento do AVC de tempo indeterminado, quatro grandes estudos na fase três sobressaem: WAKE-UP e EXTEND para trombólise intravenosa, e DAWN e DEFUSE-3 para trombectomia mecânica. A ampliação da janela terapêutica fundamenta-se nos paradigmas de incompatibilidade da imagem ponderada de difusão­recuperação da inversão atenuada por fluidos (diffusion weighted imaging­fluid-attenuated inversion recovery, DWI-FLAIR, em inglês), do núcleo isquêmico e penumbra, e clínico-radiológico. Os desafios na abordagem do AVC de tempo indeterminado envolvem a ampliação da janela terapêutica, a reprodutibilidade das modalidades de imagem no mundo real, e a identificação de novos métodos e tratamentos para essa condição. CONCLUSãO: É evidente o avanço nas possibilidades de tratamento do AVC isquêmico guiado pelos conceitos de imagem. Novos estudos nesse campo são essenciais, com necessidade de estruturar os serviços de saúde para esse novo cenário.

Rivaroxaban versus aspirin for prevention of covert brain infarcts in patients with embolic stroke of undetermined source: NAVIGATE ESUS MRI substudy.

BACKGROUND: Covert brain infarcts are associated with important neurological morbidity. Their incidence in patients with embolic stroke of undetermined source (ESUS) is unknown. AIMS: To assess the incidence of covert brain infarcts and cerebral microbleeds using MRI in a prospective substudy of the NAVIGATE ESUS randomized trial and to evaluate the effects of antithrombotic therapies. METHODS: At 87 sites in 15 countries, substudy participants were randomly assigned to receive rivaroxaban 15 mg daily or aspirin 100 mg daily and underwent brain MRI near randomization and after study termination. The primary outcome was incident brain infarct (clinical ischemic stroke or covert brain infarct). Brain infarcts and microbleeds were ascertained centrally by readers unaware of treatment. Treatment effects were estimated using logistic regression. RESULTS: Among the 718 substudy participants with interpretable, paired MRIs, the mean age was 67 years and 61% were men with a median of 52 days between the qualifying ischemic stroke and randomization and a median of seven days between randomization and baseline MRI. During the median (IQR) 11 (12) month interval between scans, clinical ischemic strokes occurred in 27 (4%) participants, while 60 (9%) of the remaining participants had an incident covert brain infarct detected by MRI. Assignment to rivaroxaban was not associated with reduction in the incidence of brain infarct (OR 0.77, 95% CI 0.49, 1.2) or of covert brain infarct among those without clinical stroke (OR 0.85, 95% CI 0.50, 1.4). New microbleeds were observed in 7% and did not differ among those assigned rivaroxaban vs. aspirin (HR 0.95, 95% CI 0.52-1.7). CONCLUSIONS: Incident covert brain infarcts occurred in twice as many ESUS patients as a clinical ischemic stroke. Treatment with rivaroxaban compared with aspirin did not significantly reduce the incidence of covert brain infarcts or increase the incidence of microbleeds, but the confidence intervals for treatment effects were wide.Registration: https://www.clinicaltrials.gov. Unique identifier: NCT02313909.

Effectiveness of statins in patients with stroke due to cervical artery dissection: A preliminary study.

BACKGROUND: Statin therapy has become one of the most important advances in stroke secondary prevention. Nevertheless, statin therapy in patients who present an ischemic stroke following cervical artery dissection (CAD) has not yet been supported by clinical evidence. This study aimed to investigate the effect of statins on neurological outcomes after a stroke due to CAD. METHODS: We conducted a prospective cohort study including consecutive patients diagnosed with a stroke due to CAD. Subjects were classified into non-statin, simvastatin 20mg, simvastatin 40mg, and high-potency statin groups. After 2 years, the functional outcome, stroke recurrence, major cardiovascular events, and mortality were assessed. RESULTS: Among the 54 patients included in our cohort, there were 16 (29.6%) patients without statins, 22 (40.7%) with simvastatin 20mg, 12 (22.2%) with simvastatin 40mg and 4 (7.5%) with high-potency statins. Using simvastatin 40mg was associated with a significantly lower incidence of stroke recurrence. Patients with simvastatin 40mg and high-potency statins presented the best functional recovery throughout the follow-up (p<.01). DISCUSSION: The use of statins in patients with CAD-related stroke may improve functional outcomes in specific cases. Statins do not prevent stroke recurrence and major cardiovascular events in this type of stroke.

Post-stroke aphasia in famous writers: when Neurology left geniuses speechless.

Aphasia is a frequent and devastating stroke complication that does not spare even great writers. In these cases, not only one of the highest cognitive functions is suddenly lost but also the act of bringing beauty into the world. Herein, we discuss the case of three writers who had to abandon their art compulsorily due to a cerebrovascular disease: Charles Baudelaire, Ralph Waldo Emerson, and Stendhal. They were magnificent writers, united by excellence in literature and an inevitable destiny that restricted their art to just a few words. They are also examples of the proximity of Neurology to Art, History, and Literature.

Effect of speech therapy intervention program for non-fluent aphasic patients after stroke.

PURPOSE: the objective of this paper is to verify the effect of speech therapy intervention program in patients with non-fluent aphasia due to stroke in language tasks related to verbal fluency in semantic and phonological categories. METHODS: Patients with aphasia due to stroke were selected to take part in this study. Two groups were formed: diagnosed patients with Broca/transcortical motor aphasia (GA), and a control group (healthy individuals). GA took a fluency verbal task (FAS, other complementary categories: phonological /p/ /l/ and semantic: "fruits" and "names"). These patients were all engaged in a language intervention program developed by the authors of this study. GA received speech therapy sessions (ten sessions lasting for an hour once a week), following a specific language program. After the sessions, the patients were re-evaluated. RESULTS: GA had statistical significant improvement in the verbal fluency task after the speech therapy program (p-value < 0,001). CONCLUSION: The speech language therapy program we proposed was efficient enough to show improvement in the results for GA in the verbal fluency task.

Neurological Manifestations of COVID-19 and the Importance of Magnetic Resonance Imaging.

A letter to the editor to discuss several uses of brain magnetic resonance imaging (MRI) in the investigation of neurological manifestations of covid-19. Described several situations in which the MRI is needed. Brain MRI is an important diagnostic method in the covid-19 scenario, to investigate possible neurological complications of the disease.

Popular knowledge of stroke in São Paulo: a cross-sectional study within the World Stroke Campaign.

BACKGROUND: Stroke is the second leading cause of death in Brazil and the main cause of disability. Inability to identify alarm signals causes delays in seeking emergency services, thereby leading to a worse prognosis. OBJECTIVES: To assess the population's knowledge of how to recognize and prevent stroke. DESIGN AND SETTING: Prospective cross-sectional study on data derived from a questionnaire that was administered during the 2016 World Stroke Campaign, launched in the city of São Paulo, Brazil. METHODS: Data on 806 interviewees were evaluated using descriptive statistics and univariate and multivariate analyses. RESULTS: Among all the interviewees, 52.1% knew how to conceptualize stroke; 70.07% knew someone who had suffered a stroke; and 29.03% listed three or more risk factors. Only 27.5% mentioned controlling high blood pressure as a preventive measure. In the event of witnessing a stroke, 57.8% would call the emergency service and 2.9% would check the timing. Less educated individuals were 5.6 times more likely (95% confidence interval, CI 3.45-9.02) to have poor knowledge of stroke, compared with the more educated group. Knowing someone who had had a stroke reduced the chances of not knowing the terms relating to the disease (odds ratio, OR = 0.56; 95% CI 0.4-0.78). CONCLUSIONS: Despite the severity and prevalence of stroke, the population still has little information on this disease. In this context, the importance of mounting campaigns to improve prevention and treatment and to contribute to healthcare policies becomes evident.